POTENT INHIBITION OF HUMAN LIVER ALDEHYDE OXIDASE BY RALOXIFENE
作者： R. Scott Obach
DOI: 10.1124/DMD.32.1.89
关键词:
摘要: The selective estrogen receptor modulator, raloxifene, has been demonstrated as a potent uncompetitive inhibitor of human liver aldehyde oxidase-catalyzed oxidation phthalazine, vanillin, and nicotine-Delta1'(5')-iminium ion, with K(i) values 0.87 to 1.4 nM. Inhibition was not time-dependent. Raloxifene also shown be noncompetitive an reduction reaction hydroxamic acid-containing compound, 51 However, raloxifene had only small effects on xanthine oxidase, enzyme related oxidase. In addition, several other compounds the same therapeutic class were examined for their potential inhibit none since IC(50) orders magnitude higher ranged from 0.29 57 micro M. examination analogs it that bisphenol structure hydrophobic group 3-position benzthiophene ring system most important element imparts inhibitory potency. relevance these data mechanistic understanding oxidase catalysis, well cause drug interactions agents which oxidase-mediated metabolism is important, such zaleplon or famciclovir, discussed.
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